Wound healing and tissue repair in humans and other warm-blooded animals are often inadequate or unacceptably slow. This is especially true in certain chronic diseases such as diabetes in the elderly, and in cancer patients. Chronic non-healing wounds create serious medical problems with infections, pain, extended hospitalization, and costly treatment.
Wound healing is a very complex process which involves the following phases or events. The first phase involves the recruitment of the proper types of white blood cells to cleanse the wound and initiate the healing response. The body seals off blood flow into the area and a white cell type called "neutrophilis" secrete toxic molecules (such as superoxide anion) into the wound to kill bacteria and induce a general inflammation.
The second phase involves the formation of granulation tissue (a mixture of fibroblasts, macrophages and new blood vessels in a loose matrix of collagen and other material) and the suppression of the inflammatory response. This occurs while while macrophages, monocytes, and other white blood cells invade to clean up tissue debris and open a path for mast cells and fibroblasts to follow and secrete angiogenic factors to attract capillary endothelial cells. There is a great proliferation of fibroblasts that secrete the structural protein collagen and glycosaminoglycans into the wound area. Reepithelialization of skin surface wounds will also commence early in the second phase.
The third and final stage involves the remodeling and formation of new connective tissue components, and wound closure.
A variety of approaches have been pursued to develop materials and methods which will aid in the healing process in warm blooded animals. One approach for the treatment of chronic wounds and skin ulcers has been the topical application of protein growth factors to the wound area (G. L. Brown et al., N Eng. J. Med., 321:76-79, 1989). Other methods include the topical application of vasoactive peptides (P. A. Janssen, J. Am. Acad. Dermatol., 21:85-90, 1989) and the systemic administration of macrophage activating agents such as tetachlorodecaoxygen (R. A. Hatz et al., Plast. and Reconst. Surg., 84:953-959, 1989). In addition, certain peptide and peptide-derivative copper(II) complexes have been shown to accelerate wound healing in animals when applied topically or by injection at the locality of the wound (U.S. Pat. Nos. 4,665,054, 4,760,051, 4,810,693 and 4,877,770).
However, even though these compounds have shown positive results in wound healing, there still exists a need in the art for compositions and methods which accelerate the healing of wounds in warm-blooded animals.